Design, Synthesis, and Antioxidant and Anti-Tyrosinase Activities of (Z)-5-Benzylidene-2-(naphthalen-1-ylamino)thiazol-4(5H)-one Analogs: In Vitro and In Vivo Insights

Molecules, Journal Year: 2025, Volume and Issue: 30(2), P. 289 - 289

Published: Jan. 13, 2025

Fifteen compounds (1–15) constructed on a hybrid structure combining β-phenyl-α,β-unsaturated carbonyl template and 2-aminothiazol-4(5H)-one scaffold were designed synthesized as potential novel anti-tyrosinase substances. Two (10 15) showed more potent inhibition against mushroom tyrosinase than kojic acid, the inhibitory activity of 10 (IC50 value: 1.60 μM) was 11 times stronger that acid. Lineweaver–Burk plots indicated these two competitive inhibitors bound to active site, which supported by in silico experiments. Compound an anti-melanogenic substance B16F10 cells without cytotoxicity. 15 exhibited most effect zebrafish larval depigmentation comparable even at concentration 200 lower. Compounds 8 strong antioxidant capacities, scavenging 2,2-diphenyl-1-picrylhydrazyl, (2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid)+ radicals, reactive oxygen species. Hybrid are therapeutic agents for skin hyperpigmentation disorders.

Language: Английский

---

Small-Molecule Tyrosinase Inhibitors for Treatment of Hyperpigmentation

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 788 - 788

Published: Feb. 8, 2025

Increasing attention is being focused on skin health currently, especially the excessive deposition of melanin in skin. Tyrosinase, rate-limiting enzyme biosynthesis, a crucial synthesis. However, existing tyrosinase inhibitors pose some degree toxicity to humans. Therefore, development more efficient and low-toxicity urgently needed. This review briefly depicts biosynthesis process crystal structure catalytic mechanism tyrosinase. The latest research progress regarding small-molecule also reviewed. Moreover, structure-function relationships are analyzed summarized. expected provide new scientific insights enable researchers explore safer potent inhibitors.

Language: Английский

---

Design, synthesis, and in vitro and in silico study of 1-benzyl-indole hybrid thiosemicarbazones as competitive tyrosinase inhibitors

RSC Advances, Journal Year: 2024, Volume and Issue: 14(39), P. 28524 - 28542

Published: Jan. 1, 2024

Developing new anti-tyrosinase drugs seems crucial for the medical and industrial fields since irregular melanin synthesis is linked to resurgence of several skin conditions, including melanoma, browning fruits vegetables. A novel series N-1 C-3 substituted indole-based thiosemicarbazones 5(a-r) are synthesized further analyzed their inhibition potential against tyrosinase enzyme through

Language: Английский

---

Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights

Molecules, Journal Year: 2025, Volume and Issue: 30(7), P. 1535 - 1535

Published: March 30, 2025

The 2,4-dihydroxyphenyl group is commonly present in the chemical structures of potent tyrosinase inhibitors. Based on this observation, a series 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole compounds 1–13 were designed and synthesized as potential Among these, 5 9 strongly inhibited mushroom activity. Particularly, compound exhibited nanomolar IC50 values regardless substrate used, whereas kojic acid yielded 15.99–26.18 μM. Kinetic studies revealed that competitively activity, findings further corroborated by silico docking analysis. In B16F10 cell-based experiments, both effectively cellular activity melanin formation. These inhibitory effects confirmed through situ assays. Compound strong antioxidant scavenging radicals, suggesting its ability to reduce production may be attributed combination properties. Additionally, five compounds, including 5, demonstrated effective depigmentation vivo zebrafish embryos, their efficacy was similar acid, even at concentrations hundreds times lower. suggest promising anti-melanogenic agents.

Language: Английский

---

Design, synthesis, and anti-melanogenic efficacy of 2-mercaptobenzoxazoles with nanomolar tyrosinase activity inhibition

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 110, P. 117832 - 117832

Published: July 9, 2024

Language: Английский

---

Exploration of Compounds with 2-Phenylbenzo[d]oxazole Scaffold as Potential Skin-Lightening Agents through Inhibition of Melanin Biosynthesis and Tyrosinase Activity

Molecules, Journal Year: 2024, Volume and Issue: 29(17), P. 4162 - 4162

Published: Sept. 2, 2024

Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[d]thiazole scaffold, we explored 1–15 2-phenylbenzo[d]oxazole, which is isosterically related to 2-phenylbenzo[d]thiazole, as novel inhibitors. Among these, 3, 8, and 13, featuring resorcinol structure, exhibited significantly stronger mushroom inhibition than kojic acid, compound 3 showing nanomolar IC50 value 0.51 μM. These results suggest that plays an important role in inhibition. Kinetic studies using Lineweaver–Burk plots demonstrated mechanisms while docking simulation indicated structure contributed binding through hydrophobic hydrogen bonding interactions. Additionally, these effectively inhibited melanin production B16F10 cells situ concentration-dependent manner. As showed no cytotoxicity epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 13 substantially higher depigmentation effects on zebrafish larvae even at 800- 400-times lower concentrations respectively. findings 2-phenylbenzo[d]oxazole promising candidate

Language: Английский

---

Exploring 2-mercapto-N-arylacetamide analogs as promising anti-melanogenic agents: In vitro and in vivo evaluation

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(37), P. 7671 - 7689

Published: Jan. 1, 2024

Based on the hypothesis that 2-mercaptoacetamide moiety chelates copper ions of tyrosinase, 2-mercapto-

Language: Английский

---

Design, Synthesis, and Anti-Melanogenic Activity of 2-Mercaptomethylbenzo[d]imidazole Derivatives Serving as Tyrosinase Inhibitors: An In Silico, In Vitro, and In Vivo Exploration

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1248 - 1248

Published: Oct. 16, 2024

2-Mercaptomethylbenzo[

Language: Английский

---